JP3826891B2 - Autosampler - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an automatic sample injection device (autosampler) used for introducing a sample into a liquid chromatograph.
[0002]
[Prior art]
In a liquid chromatograph (LC), an autosampler is used to introduce a predetermined amount of sample into a column. In the sample injection operation using the autosampler, first, a needle is inserted into a container in which a sample is placed, and a predetermined amount of sample is sucked and held in a sample loop or the like through the needle. Next, the needle is moved onto the injection port connected to the LC column, and the retained sample is injected into the injection port.
[0003]
When performing the injection operation of a sample, if a sample residue from the previous measurement adheres to the needle, it causes a measurement error due to cross contamination. Therefore, the needle is washed before performing the sample injection operation. This cleaning is usually performed by storing a cleaning liquid in a cleaning tank and immersing a needle in the cleaning liquid as described in Patent Document 1 as a conventional technique.
[0004]
[Patent Document 1]
Japanese Patent Laid-Open No. 9-127078 ([0004] to [0005], FIG. 2)
[0005]
[Problems to be solved by the invention]
According to this method, there is an advantage that the cleaning can be completed in a short time since it is only necessary to immerse the needle in the cleaning liquid. On the other hand, there is a possibility that the sample liquid diluted with the cleaning liquid may remain attached to the needle, and this residue may cause an error in the next measurement.
[0006]
In such an autosampler, there can be various cases depending on the purpose of the measurement, such as when importance is attached to the throughput, or when it is desired to perform highly accurate measurement by increasing the cleaning performance at the expense of the throughput to some extent. The conventional apparatus cannot meet such a demand.
[0007]
The present invention has been made to solve such problems, and an object of the present invention is to provide an autosampler capable of cleaning a needle by a method suitable for the purpose of measurement and the like. Is to provide.
[0008]
[Means for Solving the Problems]
The autosampler according to the present invention, which has been made to solve the above problems, is for injecting a sample into a sample introduction part communicating with a column of a liquid chromatograph,
a) a needle for sucking a sample from the sample liquid tank and injecting it into the sample introduction part;
b) a first cleaning means for cleaning the needle by immersing the needle in a cleaning liquid, wherein the cleaning liquid is not replaced during the cleaning;
c) a cleaning means for cleaning the needle by immersing the needle in the cleaning liquid, wherein the second cleaning means replaces the cleaning liquid during the cleaning;
With
The needle is washed by at least one washing means selected from the first washing means and the second washing means.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
In the autosampler of the present invention, two independent cleaning means are provided. In the first cleaning means, for example, the cleaning liquid (first cleaning liquid) is stored in a cleaning tank (first cleaning tank), and the needle is cleaned by immersing the needle. During this cleaning, the cleaning liquid in the first cleaning tank is not replaced. This replacement may be performed by injecting a new cleaning liquid into the first cleaning tank at a predetermined time while cleaning is not being performed. On the other hand, in the second cleaning means, for example, the needle is cleaned by supplying the cleaning liquid (second cleaning liquid) to the second cleaning tank after inserting the needle into the cleaning tank (second cleaning tank). By supplying this cleaning liquid, the old cleaning liquid in the second cleaning tank is discharged from the discharge port of the second cleaning tank. Accordingly, the second cleaning liquid is replaced during the cleaning in the second cleaning tank.
[0010]
In the first cleaning means, the first cleaning liquid is stored in advance in the first cleaning tank before cleaning, and only immersed for a predetermined cleaning time in the first cleaning tank. Therefore, the cleaning time is longer than when the second cleaning means is used. Can be shortened. Further, the amount of the cleaning liquid consumed in one cleaning may be smaller than when using the second cleaning means.
[0011]
On the other hand, in the second cleaning means, the cleaning liquid contaminated with the sample during the cleaning is quickly discharged from the discharge port of the second cleaning tank, and a clean cleaning liquid is newly supplied. Therefore, the residual sample in the cleaning liquid can be prevented from adhering to the needle again, and the cleaning performance can be improved as compared with the case where the first cleaning means is used.
[0012]
Thus, each of the first cleaning means and the second cleaning means has complementary advantages. In order to take advantage of these advantages, the first cleaning means and the second cleaning means are selectively used according to the application. In other words, the first cleaning means may be used when an error due to cross contamination does not matter so much or when priority is given to the throughput over the error. On the other hand, when the cross contamination sensitively affects the cleaning performance, the second cleaning means may be used giving priority to the cleaning performance.
[0013]
Since the characteristic of each cleaning means is the operation during cleaning (whether or not the cleaning liquid is replaced) as described above, when these characteristics are used as they are, the first cleaning liquid and the second cleaning liquid are of the same type. Also good. Furthermore, by using different types of the first cleaning liquid and the second cleaning liquid, it is possible to perform more appropriate cleaning by combining the cleaning operation and the type of the cleaning liquid.
[0014]
Further, both cleaning means may be used in combination during one cleaning. That is, after washing in one washing tank, washing is performed in the other washing tank. For example, when a sample containing a plurality of components adheres to the needle, first, a part of the components is removed in the first washing tank, and then the components remaining on the needle are removed in the second washing tank.
[0015]
Furthermore, the autosampler of the present invention may be provided with a switching means for selecting the cleaning liquid used in the second cleaning means from a plurality of cleaning liquids. This is a configuration in which the second cleaning liquid can be changed when the cleaning in the second cleaning means is performed using two or more types of cleaning liquids depending on the type of sample attached to the needle. As this switching means, for example, a three-way valve or the like can be used.
[0016]
【The invention's effect】
According to the present invention, the needle can be cleaned by a more appropriate cleaning method according to the purpose of measurement and the like by properly using two types of cleaning means. That is, when priority is given to throughput or the like, the needle can be cleaned in a short time using the first cleaning means, and when priority is given to reducing errors due to cross contamination, the second cleaning is performed. The needle can be washed with high capacity using the means. In addition, the type of cleaning liquid used in the second cleaning means can be switched, and the needle can be cleaned with a cleaning liquid according to the type of sample attached to the needle.
[0017]
【Example】
(1) Configuration of an embodiment of an autosampler according to the present invention An embodiment of an autosampler according to the present invention will be described. FIG. 1 is a schematic configuration diagram of the autosampler of this embodiment. The first valve 11 composed of a 7-port 6-position valve has seven ports 11a to 11g. A measuring syringe 12 is connected to the port 11a. Further, the first cleaning liquid tank 13 is connected to the port 11b, and the first cleaning tank 21 is connected to the port 11e. The second valve 14 composed of a six-way valve has six ports 14a to 14f and selectively connects adjacent ports by a switching operation. A liquid supply tube 15 for supplying a sample to a column of a liquid chromatograph is connected to the port 14a, and a liquid supply tube 16 for supplying a mobile phase to the column is connected to the port 14b. The ports 11d and 14c of the first valve 11 are connected to the ports 14d and 14e, respectively. One end of a sample loop 17 is connected to the port 14c, and a needle 18 is connected to the other end of the sample loop 17. The injection port 19 is connected to the port 14f. The needle 18 has a movable mechanism that moves between the injection port 19, the sample container 20, the first washing tank 21, and the second washing tank 22 and is inserted into each liquid.
[0018]
The first cleaning liquid in the first cleaning liquid tank 13 can be injected and stored in the first cleaning tank 21 via the measuring syringe 12, the port 11a, and the port 11e. The injection operation of the first cleaning liquid will be described later. A pump 25 for injecting the second cleaning liquid from the second cleaning liquid tank 24 to the second cleaning tank is connected to the second cleaning tank 22.
[0019]
(2) Sample injection operation of the present embodiment Before describing the cleaning of the needle that is a feature of the present invention, first, the sample injection operation of the autosampler of the present embodiment will be described. First, the second valve 14 is switched to the connection state indicated by the solid line in FIG. The needle 18 is disposed at a position on the injection port 19. The mobile phase is sent from the liquid feeding pipe 16 to the liquid feeding pipe 15 through the sample loop 17, the needle 18, and the injection port 19, and this flow path is filled with the mobile phase.
[0020]
Next, the second valve 14 is switched to the connection state indicated by the broken line in FIG. 1, and the first valve 11 is switched to the connection state indicated by the broken line in FIG. Thereby, the measuring syringe 12 and the needle 18 are connected via the ports 11a, 11d, 14d, 14c and the sample loop 17. The needle 18 moves onto the sample container 20 and is inserted into the container 20. A predetermined amount of sample is sucked from the sample container 20 to the sample loop 17 and held by the suction operation of the measuring syringe 12.
[0021]
After completion of sample aspiration, the needle 18 is returned to a position on the injection port 19. The 2nd valve | bulb 14 is returned to the connection state of the continuous line of FIG. As a result, the mobile phase is sent from the liquid feeding pipe 16 to the liquid feeding pipe 15 through the sample loop 17, the needle 18, and the injection port 19. Thus, the sample held in the sample loop 17 is supplied to the liquid chromatograph column together with the mobile phase.
[0022]
Here, since the sample adheres to the outside of the needle 18, as will be described later, the needle 18 is washed at an appropriate time before the start of the next sample injection operation.
[0023]
(3) Needle cleaning operation of the present embodiment Next, the needle cleaning operation, which is a feature of the present invention, will be described. Prior to the start of measurement, the measurer sets the following items for the needle cleaning conditions by a predetermined operation. First, the “cleaning timing” of the needle
(i) Before sample injection operation,
(ii) After sample injection operation,
(iii) both before and after the sample injection operation,
(iv) Do not wash,
Choose from. When (i) to (iii) are selected for the “cleaning timing”, further “cleaning tank to be used”
(i) Use only the first washing tank,
(ii) Use only the second washing tank,
(iii) The first and second cleaning tanks are used continuously,
(iv) Use only the second washing tank only when changing the sample type, otherwise use the first washing tank.
Choose from. When (iii) is selected for the “cleaning timing”, the “cleaning tank to be used” may be selected before and after the sample injection operation. Next, the cleaning time is set. This cleaning time sets the time for immersing the needle 18 in the cleaning liquid.
[0024]
According to the needle cleaning conditions thus set, the needle is cleaned as follows. When cleaning is performed in the first cleaning tank, first, the first valve 11 is switched to a connection state indicated by a double line in FIG. The measuring syringe 12 sucks a predetermined amount of the first cleaning liquid from the first cleaning liquid tank 13. Next, the first valve 11 is switched to the connection state indicated by the solid line in FIG. The 1st washing | cleaning liquid in the measurement syringe 12 is supplied to the 1st washing tank 21 via port 11a, 11c, 14e, 14d, 11d, 11e. The used cleaning liquid remaining in the first cleaning tank and the excessively injected cleaning liquid are discharged from the discharge port 23. Thereafter, the needle 18 is inserted into the first cleaning tank 21 and immersed in the first cleaning liquid for a set time. (Fig. 2 (a)). Thereby, the needle 18 is washed. During the cleaning, the first cleaning liquid is not supplied to the first cleaning tank 21, that is, the first cleaning liquid is not replaced. After the set time has elapsed, the needle 18 is moved to a predetermined position, and the cleaning is finished. Here, when (i) or (iv) is selected for the “cleaning tank to be used”, the predetermined position is the injection port 19 or the sample container 20. On the other hand, when (iii) is selected for the “cleaning tank to be used”, the predetermined position is the second cleaning tank 22, and the following second cleaning tank is used for subsequent cleaning.
[0025]
When cleaning is performed in the second cleaning tank 22, the needle 18 is inserted into the second cleaning tank 22, and then the pump 25 is operated to cause the second cleaning liquid to flow into the second cleaning tank 22. The needle 18 is cleaned by immersing the needle 18 in the second cleaning liquid for the set cleaning time (FIG. 2B). During this time, the second cleaning liquid flows into the second cleaning tank 22 and is discharged from the discharge port 23. Therefore, the sample adhering to the needle 18 is discharged from the discharge port 23 together with the second cleaning liquid. Thus, since the residual sample in the cleaning liquid is prevented from reattaching to the needle 18, the needle 18 can be cleaned with high capacity in the second cleaning tank. After the cleaning time has elapsed, the needle 18 is moved to a predetermined position, and the cleaning ends.
[0026]
(4) Example of proper use of cleaning tank As described above, the first cleaning tank is effective when performing simple cleaning, and the second cleaning tank is effective when high cleaning capability is required. Therefore, it is desirable to use both washing tanks by taking advantage of each advantage. In the following (a) to (c), examples of proper use are shown, and desirable settings of “cleaning tank to be used” and “cleaning timing”, which are setting items for the cleaning conditions of the needle, are shown.
[0027]
(a) When priority is given to throughput over cleaning performance In this case, (i) is selected as the “cleaning tank to be used” so that the cleaning time can be shortened. The “cleaning timing” may be any of (i) to (iii).
[0028]
(b) When the sample is denatured by the cleaning liquid When, for example, a needle to which a component such as protein is adhered is washed, this component may be denatured by the washing liquid and fixed to the needle. In this case, it is effective to select (iii) as the “cleaning tank to be used”. Here, the first cleaning liquid that does not alter the sample (the cleaning effect may be relatively low) and the second cleaning liquid that has a high cleaning effect (the sample may be altered) may be used. That is, in the first cleaning tank, components that are easily altered are removed from the needle, and then other components are sufficiently removed in the second cleaning tank. As a result, it is possible to prevent both sticking due to sample alteration and the remaining of other components. The “cleaning timing” may be any of (i) to (iii).
[0029]
(c) When importance is placed on preventing the mixing of different types of samples When measuring while changing the type of sample to be measured, the “cleaning tank to be used” may be selected from (iv). This is because the first washing tank is used to wash the needle at a high throughput while measuring the same type of sample, and the second washing tank is used only when shifting to the measurement of a different sample. Perform cleaning. Thereby, simplification of the cleaning such as an improvement in throughput can be achieved while preventing the mixing of different types of samples.
[0030]
(5) Modification In this embodiment, a second cleaning liquid switching valve can be provided so that two or more types of second cleaning liquid can be used for cleaning. An example of the configuration is shown in FIG. 1 differs from the apparatus of FIG. 1 in that a plurality of second cleaning liquid tanks 241, 242,... Are provided in order to use a plurality of types of second cleaning liquid supplied to the second cleaning tank, and the second cleaning liquid tanks. The second cleaning liquid switching valve 26 is provided for connecting the pump 25 and the pump 25. The second cleaning liquid switching valve 26 can switch the second cleaning liquid supplied to the second cleaning tank.
[0031]
Thereby, at the time of washing in the second washing tank, the switching can be performed so that the optimum second washing liquid is used for each sample used, and the washing ability can be further enhanced. For example, a basic cleaning solution may be used for an acidic sample, and an acidic cleaning solution may be used for a basic sample. An aqueous cleaning solution may be used for a water-soluble sample, and an organic solvent or the like may be used for an oil-soluble sample.
[0032]
Further, in the case of using the configuration of this modified example, when (ii) to (iv) are selected for the “cleaning tank to be used” in the setting of the cleaning condition of the needle, each sample to be further measured by the measurer The second cleaning liquid may be selected.
[Brief description of the drawings]
FIG. 1 is a schematic configuration diagram of an embodiment of an autosampler according to the present invention.
FIG. 2 is a diagram illustrating a needle cleaning operation in the present embodiment.
FIG. 3 is a schematic configuration diagram of an embodiment provided with a second cleaning liquid switching valve;
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 11 ... 1st valve 12 ... Metering syringe 13 ... 1st washing | cleaning liquid tank 14 ... 2nd valve 15, 16 ... Liquid feeding pipe 17 ... Sample loop 18 ... Needle 19 ... Injection port 20 ... Sample container 21 ... 1st washing tank 22 ... 2nd washing tank 23 ... discharge port 24, 241, 242 ... 2nd washing liquid tank 25 ... pump 26 ... 2nd washing liquid switching valve

Claims (2)

In an autosampler that injects a sample into a sample introduction part communicating with a liquid chromatograph column,
a) a needle for sucking a sample from the sample liquid tank and injecting it into the sample introduction part;
b) a first cleaning means for cleaning the needle by immersing the needle in a cleaning liquid, wherein the cleaning liquid is not replaced during the cleaning;
c) a cleaning means for cleaning the needle by immersing the needle in the cleaning liquid, wherein the second cleaning means replaces the cleaning liquid during the cleaning;
With
An autosampler, wherein the needle is washed by at least one washing means selected from the first washing means and the second washing means. The autosampler according to claim 1, further comprising a switching unit that selects a cleaning liquid to be used in the second cleaning unit from a plurality of cleaning liquids.

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